A Chemosensory GPCR as a Potential Target to Control the Root-Knot Nematode Meloidogyne incognita Parasitism in Plants

Molecules. 2019 Oct 22;24(20):3798. doi: 10.3390/molecules24203798.

Abstract

Root-knot nematodes (RKN), from the Meloidogyne genus, have a worldwide distribution and cause severe economic damage to many life-sustaining crops. Because of their lack of specificity and danger to the environment, most chemical nematicides have been banned from use. Thus, there is a great need for new and safe compounds to control RKN. Such research involves identifying beforehand the nematode proteins essential to the invasion. Since G protein-coupled receptors GPCRs are the target of a large number of drugs, we have focused our research on the identification of putative nematode GPCRs such as those capable of controlling the movement of the parasite towards (or within) its host. A datamining procedure applied to the genome of Meloidogyne incognita allowed us to identify a GPCR, belonging to the neuropeptide GPCR family that can serve as a target to carry out a virtual screening campaign. We reconstructed a 3D model of this receptor by homology modeling and validated it through extensive molecular dynamics simulations. This model was used for large scale molecular dockings which produced a filtered limited set of putative antagonists for this GPCR. Preliminary experiments using these selected molecules allowed the identification of an active compound, namely C260-2124, from the ChemDiv provider, which can serve as a starting point for further investigations.

Keywords: Meloidogyne incognita; homology modelling; molecular dynamics; virtual screening.

MeSH terms

  • Animals
  • Antinematodal Agents / chemistry*
  • Antinematodal Agents / metabolism
  • Antinematodal Agents / pharmacology
  • Genome, Helminth
  • Helminth Proteins / antagonists & inhibitors
  • Helminth Proteins / chemistry*
  • Helminth Proteins / genetics*
  • Host-Parasite Interactions / genetics
  • Lycopersicon esculentum / parasitology
  • Molecular Dynamics Simulation
  • Phylogeny
  • Plant Diseases / parasitology
  • Plant Diseases / prevention & control
  • Plant Roots / parasitology
  • Protein Structure, Secondary
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / genetics*
  • Tylenchoidea / genetics*

Substances

  • Antinematodal Agents
  • Helminth Proteins
  • Receptors, G-Protein-Coupled